Process for the preparation of ketones

ABSTRACT

A process for the preparation of a ketone which comprises reacting the corresponding secondary alkanol with a solubilized stable free radical nitroxide having the formula: ##STR1## wherein each of R 1 , R 2 , R 3  and R 4  is an alkyl, aryl or heteroatom substituted alkyl group having 1 to about 15 carbon atoms and each of R 5  and R 6  is alkyl, hydrogen, aryl or a substituted heteroatom, and nitric acid in the presence of an oxidant at a temperature in the range of from about -10° C. to about 80° C. and thereafter separating out the ketone.

FIELD OF THE INVENTION

This invention relates to a process for the preparation of ketones bythe oxidation of the corresponding secondary alkanols in the presence ofa stable free radical nitroxide, nitric acid and an oxidant.

BACKGROUND OF THE INVENTION

It is known to use nitroxyl radicals/oxoammonium salts in the oxidationof primary alcohols to produce aldehydes and acids and the oxidation ofsecondary alcohols to produce ketones (Journal of Organic Chemistry,vol. 52 (12), pp. 2559-2562 and Journal of Organic Chemistry, vol. 55,1990, pp. 462-466). The primary products produced in these processes arealdehydes and the stoichiometrically consumed oxidant is hypochlorite.

It is reported in the open literature that primary aliphatic alcoholscan be converted to aldehydes, but only in 30-40% yields in the presenceof catalytic amounts of cuprous chloride,2,2,6,6,-tetramethylpiperidine-1-oxyl, and atmoshperic oxygen (Journalof American Chemical Society, 1984, 106, pp. 3374). It is also knownthat higher yields of aldehydes can be obtained if stoichiometricamounts of cupric or ferric salts are used instead of catalytic amountsof the cuprous salts (Pure and Applied Chemistry, vol. 62(2), 1990, pp.217-222).

OBJECTS OF THE INVENTION

It is an object of this invention to produce ketones in high yields andwith high selectivities from secondary alkanols.

It has been found that ketones can be produced in high yields and withhigh selectivities by using catalytic amounts of a stable free radicalnitroxide, nitric acid and an oxidant.

SUMMARY OF THE INVENTION

This invention relates to a process for the preparation of a ketonewhich comprises reacting the corresponding secondary alkanol with asolubilized stable free radical nitroxide having the formula: ##STR2##wherein each of R₁, R₂, R₃ and R₄ is an alkyl, aryl or heteroatomsubstituted alkyl group having 1 to about 15 carbon atoms and each of R₅and R₆ is alkyl, hydrogen, aryl or a substituted heteroatom, and nitricacid in the presence of an oxidant at a temperature in the range of fromabout -10° C. to about 80° C. and thereafter separating out the ketone.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present process converts secondary alkanols to the correspondingketones by contacting the secondary alkanol with a solubilized stablefree radical nitroxide and nitric acid in the presence of an oxidant ata temperature in the range of from about -10° C. to about 80° C.

The secondary alkanol reactant suitably comprises one or more secondaryalkanols having a carbon number in the range of from about 3 to about45. An secondary alkanol consisting essentially of secondary,mono-alkanols is preferred. Most preferably, the secondary alkanolreactant consists essentially of one or more C₆ to C₃₀ secondarymono-alkanols. Preference can also be expressed for secondary alkanolshaving from 8 to about 22 carbon atoms, with C₁₀ to C₂₀ secondaryalkanols considered more preferred and C₁₁ to C₁₈ secondary alkanolsconsidered most preferred. As a general rule, the carbon chains of thesecondary alkanols may be of either branched or linear (straight-chain)structure, although preference further exists for secondary alkanolreactants in which greater than about 50 percent, more preferablygreater than about 70 percent and most preferably greater than about 90percent of the molecules are of linear (straight-chain) carbonstructure. In large part, such preferences relate more to the utilityand value of the products than to the operability or performance of theprocess of the invention.

The general suitability of such secondary alkanols as reactants inoxidation reactions is well recognized in the art. Examples of specificsecondary alkanols and commercially available secondary alkanols andsecondary alkanol mixtures within this class are also well known.Commercially available mixtures of secondary alkanols prepared via theoxidation of paraffins, and from internal olefins and alpha-olefinmixtures via sulfation and hydrolysis reactions are particularlysuitable.

Suitable examples of C₁₀ to C₂₀ secondary alkanols which arecommercially available include Tergitol 15, a trademark of and sold byUnion Carbide, in which the main components are C₁₁ to C₁₅ compounds.,Tergitol 45, in which the main components are C₁₄ to C₁₅ compounds;Softanol 24, a trademark of and sold by Nippon Shokubai Kagaku KogyoCo., Ltd., in which the main components are C₁₂ to C₁₄ compounds, andthe like. Examples of suitable secondary alkanols having lower carbonnumbers include isopropanol, 2-butanol, 2-pentanol, 3-pentanol,2-hexanol, 3-hexanol, 2-octanol, 3-octanol and the like.

The term "stable free radical nitroxide" as used herein shall mean afree radical nitroxide that can be prepared by conventional chemicalmethods and will exist long enough to be used in a subsequent chemicalreaction or examined in a static system by normal methods ofspectroscopy. Generally, the stable free radical nitroxides of thepresent invention have a half life of at least one year. The term"stable free radical" shall also be understood to include the presursorto a stable free radical from which the stable free radical may beproduced in situ.

The stable free radical nitroxides, as used in the present process, areprecursors to catalysts, i.e., oxoammonium salts, active for theoxidation of secondary alkanols to the corresponding ketones. Thesecatalysts are generated in situ by the oxidation of a stable freeradical nitroxide to an oxoammonium salt with an oxygen-containingoxidant. The stable free radical nitroxide can be obtained by theoxidation of secondary amines or hydroxylamines.

The stable free radical nitroxides which are suitable for use in theinstant invention have the formula: ##STR3## wherein each of R₁, R₂, R₃and R₄ is an alkyl, aryl or heteroatom substituted alkyl group having 1to about 15 carbon atoms and no hydrogen is bound to the remainingvalences on the carbon atoms bound to the nitrogen, and each of R₅ andR₆ is alkyl, hydrogen, aryl or a substituted heteroatom. As used herein,the term "alkyl" is meant to include cycloalkyl. The alkyl (orheteroatom substituted) groups R₁₋ R₄ may be the same or different, andpreferably contain 1 to 15 carbon atoms. Preferably, R₁₋ R₄ are methyl,ethyl, or propyl groups. In addition to hydrogen, the heteroatomsubstituents may include, halogen, oxygen, nitrogen and the like.Preferably, one of R₅ and R₆ is hydrogen and the other is a substitutedheteroatom which does not interfere with the reaction. Suitablesubstituted heteroatoms include ##STR4## polymer and the like.

In a preferred embodiment, the nitroxide is selected from the groupconsisting of 2,2,6,6-tetramethyl-piperidine-1-oxyl, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl,4-oxo-2,2,6,6-tetramethyl-piperidine-1oxyl,2,2,6,6-tetramethyl-piperidine-1-oxyl-4-sulfate,4-alkoxy-2,2,6,6-tetramethyl-piperidine-1-oxyl and mixtures thereof,with 2,2,6,6-tetramethyl-piperidine-1-oxyl,2,2,6,6-tetramethyl-piperidine-1oxyl-4-sulfate, and4-alkoxy-2,2,6,6-tetramethyl-piperidine-1-oxyl being particularlypreferred.

As used herein, the term "nitric acid" refers to nitric acid, fumingnitric acid or nitrous acid generated by contacting alkali metal nitritewith mineral acid. The nitric acid suitable for use in the presentinvention typically has a concentration in the range of from about 50percent to about 100 percent, preferably about 70 percent. Generally, anamount of nitric acid in the range of from about 5 mole percent to about100 mole percent, basis the moles of starting secondary alkanol is used.The nitric acid is typically added to the reaction mixture after all ofthe other reactants have been added, but prior to the addition of theoxidant. While not wishing to be bound by any particular theory, it isbelieved that nitrogen oxides (NO_(x)) are generated in the reaction andare the active species in the reaction.

The oxidants suitable for use in the instant invention are thosecompounds which, in the presence of nitric acid, are capable ofoxidizing the stable free radical nitroxide to the oxoammonium salt.Suitable oxidants include oxygen or an oxygen-containing gas such asair. Whereas pure oxygen is preferred to accomplish the desiredconversion, the oxygen can be diluted with an inert gas such asnitrogen, helium, argon, or other similar gas. For purposes ofincreasing the reaction rate, higher O₂ pressures such as, for example,1000 psi can be utilized. In a preferred embodiment, pure oxygen is usedas the oxidant and it is bubbled into the reaction solution atatmoshperic pressure. It is critical that the flow of the oxidant oroxygen-containing gas be continuous throughout the process in order tokeep the reaction going. If the flow of oxygen is stopped during thecourse of the reaction, the reaction rate can be lowered.

The amounts and concentrations of the reactants utilized in the processof the instant invention can vary within wide ranges. The amount ofstable free radical nitroxide is typically in the range of from about 1mole percent to about 50 mole percent, preferably from about 5 molepercent to about 30 mole percent, and more preferably from about 10 molepercent to about 20 mole percent, basis the moles of starting secondaryalkanol. Generally, the amount of nitric acid utilized will be in therange of from about 5 mole percent to about 100 mole percent, preferablyfrom about 25 mole percent to about 50 mole percent, basis the weight ofthe starting secondary alkanol.

The reaction in the instant invention may be carried out in the presenceof a solvent or in the absence of a solvent. When the reaction iscarried out in the presence of a solvent, the solvent is typically onein which the secondary alkanol is readily soluble. Solvents which aremost suitable are those which are inert in the reaction. The solvent maybe added to the reaction mixture of secondary alkanol and nitroxide or,alternatively, the nitroxide may be dissolved in the solvent prior toaddition of the nitroxide to the reaction medium. The solvent istypically selected from the group consisting of acetonitrile, tertiaryalcohols such as tertiary butyl alcohol and tertiary amyl alcohol,hydrocarbons such as heptane, glyme, dichloromethane, chlorobenzene,ethyl acetate and mixtures thereof, with dichloromethane and tertiarybutyl alcohol being preferred. The amount of solvent utilized in theprocess is generally from about 20:1 to about 0.5:1, preferably fromabout 10:1 to about 5:1, basis the weight of the starting secondaryalkanol.

The process of the present invention is typically conducted under mildconditions, with good results being obtained using a temperature in therange of from about -10° C. to about 80° C., preferably from about 20°C. to about 60° C., more preferably from about 30° C. to about 45° C.,and most preferably from about 35° C. to about 40° C. Reaction pressuresare not critical although higher pressures result in increased reactionrates. Pressures in the range of from about atmospheric pressure up toabout 1000 psig can be employed with good results.

The process of the instant invention can be carried out either batchwiseor continuously, using a stirrer equipped reactor or other well knowncontacting technique to achieve adequate mixing. Preferred reactionconditions, e.g., temperature, pressure, flow rates, etc., vary somewhatdepending on the specific nitroxide utilized, the solvent utilized, andon the concentration of the nitroxide.

The process of the instant invention can be carried out in a variety ofways. For example, 0.032 moles of secondary alkanol, 0.006 moles of thenitroxide, and 25 milliliters of solvent may be added to the reactionvessel, followed by the addition of 0.016 moles of 70% nitric acid andan atomospheric O₂ stream. In a preferred embodiment, the reaction iscarried out by adding the secondary alkanol, the nitroxide, the solventand the nitric acid and then bubbling an oxidizing gas through themixture. Following the reaction, the product may be separated from thereaction mixture using conventional procedures such as extraction usinga suitable extraction solvent such as, for example, ethyl acetate.,evaporation wherein the solvent is stripped from the reaction mixture byusing heat or vacuum. The reaction product can be purified by a numberof conventional means such as, for example, distillation or othermethods known in the art.

Depending upon process conditions and the nitroxide used, the yields ofketone obtained by this invention are typically about 85% of startingsecondary alkanol material being converted. The products produced by theinstant process can be used in a variety of applications. For example,these products can be used as solvents, or as intermediates to produceamines or ethers.

The ranges and limitations provided in the instant specification andclaims are those which are believed to particularly point out anddistinctly claim the present invention. It is, however, understood thatother ranges and limitations which perform substantially the samefunction in the same or substantially the same manner to obtain the sameor substantially the same result are intended to be within the scope ofthe instant invention as defined by the instant specification andclaims.

The process of this invention will be further described by the followingembodiments which are provided for illustration and are not to beconstrued as limiting the invention.

ILLUSTRATIVE EMBODIMENTS EXAMPLE 1

4.2 Grams of 2-octanol, 1 gram of 2,2,6,6-tetramethyl-piperidine-1-oxyl,25 milliliters of dichloromethane, and 1 gram of 70% nitric acid werecharged to a 100 milliliter round bottomed flask. An O₂ stream was thenbubbled through the mixture at atmospheric pressure. The reaction washeld at a temperature of 35° C. over a 4 hour period. The results arepresented in Table I.

EXAMPLE 2

4.2 Grams of 2-octanol, 1 gram of 2,2,6,6-tetramethyl-piperidine-1-oxyl,25 milliliters of tertiary butyl alcohol, and 1 gram of 70% nitric acidwere charged to a 100 milliliter round bottomed flask. An O₂ stream wasthen bubbled through the mixture at atmospheric pressure. To thismixture was added O₂ . The reaction was held at a temperature of 35° C.over a 6 hour period. The results are presented in Table I.

EXAMPLE 3

4.2 Grams of 2-octanol, 1 gram of 2,2,6,6-tetramethyl-piperidine-1-oxyl,25 milliliters of heptane and 1 gram of 70% nitric acid were charged toa 100 milliliter round bottomed flask. An O₂ stream was then bubbledthrough the mixture at atmospheric pressure. To this mixture was addedO₂. The reaction was held at a temperature over of 35° C. a 6 hourperiod. The results are presented in Table I.

EXAMPLE 4

4.2 Grams of 2-octanol, 1 gram of 2,2,6,6-tetramethyl-piperidine-1-oxyl,25 milliliters of heptane and 1 gram of 70% nitric acid were charged toa 100 milliliter round bottomed flask. Air was then bubbled through themixture at atmospheric pressure. The reaction was held at a temperatureover of 35° C. a 6 hour period. The results are presented in Table I.

COMPARATIVE EXAMPLE A

Comparative Example A was carried out in a manner similar to Example 1except that no nitroxide was used. The results are presented in Table I.

COMPARATIVE EXAMPLE B

Comparative Example B was carried out in a manner similar to Example 1except that no nitric acid was used. The results are presented in TableI.

As can be seen in Table I, both notroxide and nitric acid are essentialto the oxidation of secondary alcohols to ketones.

                  TABLE I                                                         ______________________________________                                        Oxidation Of Secondary Alkanols to Ketones                                                  % Starting                                                                    Alkanol %                                                                     Remaining                                                                             Ketones                                                 ______________________________________                                        Example 1       12.1      87.9                                                Example 2       10.4      89.6                                                Example 3       13.8      86.2                                                Example 4       22.1      77.9                                                Comparative     94.4      5.6                                                 Example A                                                                     Comparative     100       0                                                   Example B                                                                     ______________________________________                                    

What is claimed is:
 1. A process for the preparation of a ketone whichcomprises reacting the corresponding secondary alkanol with asolubilized stable free radical nitroxide having the formula: ##STR5##wherein each of R₁, R₂, R₃ and R₄ is an alkyl, aryl or heteroatomsubstituted alkyl group having 1 to about 15 carbon atoms and each of R₅and R₆ is alkyl, hydrogen, aryl or a substituted heteroatom, and nitricacid in the presence of an oxidant at a temperature in the range of fromabout -10° C. to about 80° C. and thereafter separating out the ketone.2. The process of claim 1 wherein the solubilized stable free radicalnitroxide is selected from the group consisting of2,2,6,6-tetramethyl-piperidine-1-oxyl,4-hydroxy-2,2,6,6-tetramethyl-piperidine -1-oxyl,4-oxo-2,2,6,6-tetramethyl-piperidine-1-oxyl,2,2,6,6-tetramethyl-piperidine-1-oxyl-4-sulfate,4-alkoxy-2,2,6,6-tetramethyl-piperidine-1-oxyl and mixtures thereof. 3.The process of claim 2 wherein the solubilized stable free radicalnitroxide is selected from the group consisting of2,2,6,6-tetramethyl-piperidine-1-oxyl,2,2,6,6-tetramethyl-piperidine-1-oxyl-4-sulfate,4-alkoxy-2,2,6,6-tetramethyl-piperidine-1-oxyl and mixtures thereof. 4.The process of claim 1 wherein the solubilized stable free radicalnitroxide is dissolved in a solvent selected from the group consistingof acetonitrile, tertiary butyl alcohol, tertiary amyl alcohol, heptane,dichloromethane, glyme, chlorobenzene, ethyl acetate and mixturesthereof.
 5. The process of claim 4 wherein the stable free radicalnitroxide is dissolved in a solvent selected from the group consistingof dichloromethane, tertiary butyl alcohol and mixtures thereof.
 6. Theprocess of claim 1 wherein said nitric acid has a concentration in therange of from about 50 percent to about 100 percent.
 7. The process ofclaim 6 wherein said nitric acid has a concentration in of about 70percent.
 8. The process of claim 1 wherein said secondary alkanol iscontacted with said solubilized stable free radical nitroxide, followedby the addition thereto of said nitric acid and said oxidant.
 9. Theprocess of claim 8 wherein the amount of solubilized stable free radicalnitroxide is in the range of from about 1 mole percent to about 50 molepercent, basis the number of moles of starting secondary alkanol. 10.The process of claim 9 wherein the amount of solubilized stable freeradical nitroxide is in the range of from about 5 mole percent to about30 mole percent, basis the number of moles of starting secondaryalkanol.
 11. The process of claim 8 wherein the amount of nitric acid isin the range of from about 5 mole percent to about 100 mole percent,basis the number of moles of starting secondary alkanol.
 12. The processof claim 1 wherein said oxidant is an oxygen-containing gas.
 13. Theprocess of claim 12 wherein said oxygen-containing gas is selected fromthe group consisting of pure oxygen and air.
 14. The process of claim 13wherein said oxygen-containing gas is pure oxygen.
 15. The process ofclaim 1 wherein said process is carried out at a temperature in therange of from about 20° C. to about 60° C. and at atmospheric pressure.16. The process of claim 15 wherein said process is carried out at atemperature in the range of from about 30° C. to about 45° C. and atatmospheric pressure.